Evaluate Vaccine Against Chickenpox and a Combined Vaccine Against 4 Viral Childhood Diseases: Measles, Mumps, Rubella and Chickenpox

Study in Healthy Children (<2 Years) to Evaluate the Safety and Efficacy of GSK Biologicals' Live Attenuated Varicella Vaccine (VarilrixTM) and of GSK Biologicals' Combined Measles-Mumps-Rubella-Varicella Vaccine

An observer-blind study to evaluate GlaxoSmithKline Biologicals' live attenuated varicella vaccine and GlaxoSmithKline Biologicals' combined measles-mumps-rubella-varicella vaccine in the prevention of varicella disease in children. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Study Overview

• Status: Completed
• Conditions: Varicella; Chickenpox Vaccines
• Intervention / Treatment: Biological: Priorix-tetra™; Biological: Priorix™; Biological: Varilrix™

Detailed Description

According to treatment group allocation, participants will receive study vaccines and be followed for antibody titres and occurrence of varicella disease.

This study is conducted in 2 phases. Phase A includes the vaccination period and an observation period for efficacy. The efficacy endpoints will be evaluated over at least two years after vaccination. During this period, the immunogenicity endpoints will be evaluated with respect to the immune response 43 days after vaccination and the persistence of antibodies over two years to varicella (for all subjects) and to measles, mumps and rubella (for a subset of subjects). Regarding the safety endpoints, SAEs (including any complicated varicella cases if observed) will be assessed for all subjects during the whole Phase A duration, whereas, solicited (local and general) and unsolicited adverse events will be assessed in a subset of subjects within a 43-day period after vaccination.

Phase B is an extension of Phase A. It is a long-term follow-up until Year 10 to examine the long-term efficacy of the study vaccines against clinical varicella disease as well as the long-term persistence of antibodies to varicella (for all subjects) and to measles, mumps and rubella (in a subset of subjects) after vaccination.

• Study Type: Interventional
• Enrollment (Actual): 5803
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 628 00
    • GSK Investigational Site
  • Chomutov, Czechia, 43003
    • GSK Investigational Site
  • Decin, Czechia, 405 01
    • GSK Investigational Site
  • Havlickuv Brod, Czechia, 580 22
    • GSK Investigational Site
  • Hradec Kralove, Czechia, 500 01
    • GSK Investigational Site
  • Humpolec, Czechia, 396 01
    • GSK Investigational Site
  • Jindrichuv Hradec, Czechia, 377 01
    • GSK Investigational Site
  • Kolin, Czechia, 28002
    • GSK Investigational Site
  • Liberec, Czechia, 46015
    • GSK Investigational Site
  • Moravska Ostrava, Czechia, 702 00
    • GSK Investigational Site
  • Nachod, Czechia, 547 01
    • GSK Investigational Site
  • Ostrava, Czechia, 728 92
    • GSK Investigational Site
  • Pardubice, Czechia, 532 03
    • GSK Investigational Site
  • Plzen, Czechia, 305 99
    • GSK Investigational Site
  • Praha 4, Czechia, 140 00
    • GSK Investigational Site
  • Praha 4, Czechia, 14200
    • GSK Investigational Site
  • Praha 5, Czechia, 150 00
    • GSK Investigational Site
  • Praha 6, Czechia, 160 00
    • GSK Investigational Site
  • Praha 9, Czechia, 190 00
    • GSK Investigational Site
  • Znojmo, Czechia
    • GSK Investigational Site
• Greece
  • Arta, Greece, 471 00
    • GSK Investigational Site
  • Athens, Greece, 115 22
    • GSK Investigational Site
  • Athens, Greece, 115 27
    • GSK Investigational Site
  • Athens, Greece, 25236
    • GSK Investigational Site
  • Giannitsa, Greece, 581 00
    • GSK Investigational Site
  • Karditsa, Greece, 43100
    • GSK Investigational Site
  • Komotini, Greece, 69 100
    • GSK Investigational Site
  • Ptolemaida, Greece, 50200
    • GSK Investigational Site
  • Thessaloniki, Greece, 54636
    • GSK Investigational Site
  • Tripolis, Greece, 22100
    • GSK Investigational Site
  • Veria, Greece, 591 00
    • GSK Investigational Site
• Italy
  • Campania
    • Quarto (NA), Campania, Italy, 80010
      • GSK Investigational Site
  • Emilia-Romagna
    • Ferrara, Emilia-Romagna, Italy, 44100
      • GSK Investigational Site
  • Friuli-Venezia-Giulia
    • Udine, Friuli-Venezia-Giulia, Italy, 33100
      • GSK Investigational Site
  • Liguria
    • Genova, Liguria, Italy, 16132
      • GSK Investigational Site
  • Lombardia
    • Milano, Lombardia, Italy, 20122
      • GSK Investigational Site
  • Piemonte
    • Novara, Piemonte, Italy, 28100
      • GSK Investigational Site
  • Sardegna
    • Alghero (SS), Sardegna, Italy, 07041
      • GSK Investigational Site
    • Ozieri (SS), Sardegna, Italy, 07014
      • GSK Investigational Site
  • Toscana
    • Firenze, Toscana, Italy, 50139
      • GSK Investigational Site
• Lithuania
  • Alytus, Lithuania, LT-63164
    • GSK Investigational Site
  • Kaunas, Lithuania, LT-48259
    • GSK Investigational Site
  • Klaipeda, Lithuania, LT-94007
    • GSK Investigational Site
  • Panevezys, Lithuania, LT-37355
    • GSK Investigational Site
  • Siauliai, Lithuania, LT-76346
    • GSK Investigational Site
  • Vilnius, Lithuania, LT-02169
    • GSK Investigational Site
  • Vilnius, Lithuania, LT -10207
    • GSK Investigational Site
  • Vilnius, Lithuania, LT-11200
    • GSK Investigational Site
• Norway
  • Bekkestua, Norway, 1319
    • GSK Investigational Site
  • Moelv, Norway, N-2390
    • GSK Investigational Site
  • Paradis, Norway, 5231
    • GSK Investigational Site
  • Skien, Norway, N-03730
    • GSK Investigational Site
  • Trondheim, Norway, N-7036
    • GSK Investigational Site
• Poland
  • Bydgoszcz, Poland, 85-021
    • GSK Investigational Site
  • Debica, Poland, 39-200
    • GSK Investigational Site
  • Krakow, Poland, 31-202
    • GSK Investigational Site
  • Olesnica, Poland, 56-400
    • GSK Investigational Site
  • Poznan, Poland, 61-709
    • GSK Investigational Site
  • Siemianowice Slaskie, Poland, 41-103
    • GSK Investigational Site
  • Tarnow, Poland, 33-100
    • GSK Investigational Site
  • Trzebnica, Poland, 55-100
    • GSK Investigational Site
  • Wesola, Poland, 05-077
    • GSK Investigational Site
  • Wroclaw, Poland, 52-312
    • GSK Investigational Site
• Romania
  • Brasov, Romania
    • GSK Investigational Site
  • Bucharest, Romania, 077190
    • GSK Investigational Site
  • Bucharest, Romania, 050098
    • GSK Investigational Site
  • Bucharest, Romania, 22102
    • GSK Investigational Site
  • Bucharest, Romania, 20395
    • GSK Investigational Site
  • Cluj-Napoca, Romania, 400217
    • GSK Investigational Site
  • Constanta, Romania, 900709
    • GSK Investigational Site
  • Sibiu, Romania
    • GSK Investigational Site
  • Timisoara, Romania, 300593
    • GSK Investigational Site
• Russian Federation
  • Ekaterinburg, Russian Federation, 620085
    • GSK Investigational Site
  • Ekaterinburg, Russian Federation, 620109
    • GSK Investigational Site
  • Ivanteevka Moscow Region, Russian Federation, 141280
    • GSK Investigational Site
  • Moscow, Russian Federation, 115446
    • GSK Investigational Site
  • Moscow, Russian Federation, 119991
    • GSK Investigational Site
  • Moscow, Russian Federation, 115 478
    • GSK Investigational Site
  • Murmansk, Russian Federation, 183046
    • GSK Investigational Site
  • Novokuznetsk, Russian Federation, 654063
    • GSK Investigational Site
  • Novosibirsk, Russian Federation, 630112
    • GSK Investigational Site
  • Samara, Russian Federation, 443079
    • GSK Investigational Site
  • Sankt-Peterburg, Russian Federation, 191123
    • GSK Investigational Site
  • Saratov, Russian Federation, 410010
    • GSK Investigational Site
  • Tomsk, Russian Federation, 634001
    • GSK Investigational Site
  • Volgograd, Russian Federation, 400130
    • GSK Investigational Site
• Slovakia
  • Bratislava, Slovakia, 841 08
    • GSK Investigational Site
  • Bratislava, Slovakia, 851 05
    • GSK Investigational Site
  • Dlha nad Oravou, Slovakia, 027 55
    • GSK Investigational Site
  • Dolny Kubin, Slovakia, 026 01
    • GSK Investigational Site
  • Dubnica Nad Vahom, Slovakia, 018 41
    • GSK Investigational Site
  • Nova Dubnica, Slovakia, 018 51
    • GSK Investigational Site
  • Nove Mesto nad Vahom, Slovakia, 915 01
    • GSK Investigational Site
  • Nove Zamky, Slovakia, 940 01
    • GSK Investigational Site
  • Puchov, Slovakia, 020 01
    • GSK Investigational Site
  • Ruzomberok, Slovakia, 034 01
    • GSK Investigational Site
  • Sturovo, Slovakia, 943 01
    • GSK Investigational Site
  • Surany, Slovakia, 942 18
    • GSK Investigational Site
  • Trencin, Slovakia, 911 01
    • GSK Investigational Site
• Sweden
  • Linköping, Sweden, SE-581 85
    • GSK Investigational Site
  • Malmö, Sweden, 205 02
    • GSK Investigational Site
  • Norrköping, Sweden, SE-602 39
    • GSK Investigational Site
  • Umeå, Sweden, SE-901 85
    • GSK Investigational Site
  • Örebro, Sweden, SE-702 11
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 months to 1 year (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol for the whole duration of the study.
• Male or female subject between 12 and 22 months of age at the time of the first vaccination.
• Subjects free of obvious health problems, as established by medical history and physical examination before entering the study.
• Written informed consent obtained from the parents/guardians of the subject after they have been informed on the risks and benefits of the study, in a language they clearly understand and before performance of any study procedure.
• Subjects whose parents/guardians have direct access to telephone/mobile phone.

• Subjects:

  1. with at least one sibling (with negative history of varicella disease/vaccination) at home, or
  2. attending day care center, or
  3. attending childminders, i.e. someone taking care of several children, or
  4. who are in contact for at least once a week with other children without a known positive history of varicella disease/vaccination, while playing in close physical contact for more than 5 minutes.

Exclusion criteria:

• Previous vaccination against measles, mumps, rubella and/or varicella.
• History of previous measles, mumps, rubella and/or varicella/ herpes zoster diseases.
• Known exposure to measles, mumps, rubella and/or varicella/herpes zoster within 30 days prior to the start of the study.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
• Administration of immunoglobulins and/or any blood products within three months prior to the first vaccine dose or planned administration during the study period.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical.
• Family history of congenital or hereditary immunodeficiency.
• History of allergic diseases or reactions likely to be exacerbated by any component of the vaccines, including systemic allergy to egg proteins or neomycin.
• Major congenital defects or serious chronic illness.
• Residence in the same household as newborns (0-4 weeks of age), pregnant women who are varicella-susceptible, persons with a known immunodeficiency or any other persons at high risk for varicella.
• History of any neurologic disorders or seizures.
• Use of any investigational or non-registered product (drug/vaccine other than the study vaccines) within 14 days prior to vaccination and planned use during the study period.

Additional exclusion criteria for subjects included in the subset:

- Administration of a licensed vaccine within 14 days prior to vaccination and planned use until approximately 42 days after the last study vaccine dose (Day 84) with the exception of oral polio vaccine (OPV).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MMRV Group; Subjects in this group received 2 doses of Priorix-Tetra vaccine, administered subcutaneously in the deltoid region of the left arm, one at Day 0 (Visit 1) and the other at Day 42 (Visit 2).	Biological: Priorix-tetra™; 2 doses administered subcutaneously, one at Day 0 and the other at Day 42 to subjects in MMRV Group
Experimental: OKAH Group; Subjects in this group received 1 dose of Priorix at Day 0 (Visit 1) and 1 dose of Varilrix at Day 42 (Visit 2). Both vaccines were administered subcutaneously in the deltoid region of the left arm.	Biological: Priorix™; 2 doses administered subcutaneously, one at Day 0 and the other at Day 42 to subjects in MMR Group and one dose administered subcutaneously at Day 0 to subjects in OKAH Group; Biological: Varilrix™; 1 dose administered subcutaneously at Day 42 to subjects in OKAH Group
Active Comparator: MMR Group; Subjects in this group received 2 doses of Priorix, administered subcutaneously in the deltoid region of the left arm, one at Day 0 (Visit 1) and the other at Day 42 (Visit 2).	Biological: Priorix™; 2 doses administered subcutaneously, one at Day 0 and the other at Day 42 to subjects in MMR Group and one dose administered subcutaneously at Day 0 to subjects in OKAH Group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase A: Number of Subjects With Confirmed Varicella Case	Confirmed varicella case = A case that met the clinical case definition [an illness with acute onset of diffuse, generalized maculopapulovesicular rash (i.e. spots, papules and/or vesicles) without other apparent cause] at least in the opinion of the investigator and was confirmed by laboratory test [Polymerase Chain Reaction (PCR) (+)] OR a case that met the clinical definition confirmed by the Independent Data Monitoring Committee (IDMC) and was epidemiologically linked [Epi (+)] to a valid index case.	From 42 days post dose 2 until the end of Phase A

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase A: Number of Subjects With Moderate or Severe Confirmed Varicella Case	Confirmed varicella case: A case that met the clinical case definition at least in the opinion of the investigator and was confirmed by laboratory test [PCR (+)] OR a case that met the clinical definition confirmed by the IDMC and was epidemiologically linked [Epi (+)] to a valid index case. Moderately severe disease: 8-15 points; severe disease: ≥ 16 points (scored by IDMC using the modified Vázquez scale).	From 42 days post dose 2 until the end of Phase A
Phase A: Number of Subjects With Probable or Confirmed Varicella Case	Probable or confirmed varicella case = A case that met the clinical case definition (as determined by the IDMC) but was not laboratory confirmed [PCR (-)] AND was not epidemiologically linked [Epi (-)] to another probable or confirmed case.	From 42 days post dose 2 until the end of Phase A
Phase A: Immune Response to Varicella Vaccine With Respect to Anti-Varicella Zoster Virus (Anti-VZV) Antibody Concentrations	Anti-VZV antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in milliinternational units per milliliter (mIU/mL).	At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
Phase A: Number of Subjects With Seroconversion/Seroresponse to VZV	Seronegative (S-) = Subjects with antibody concentration less than (<) 25 mIU/mL prior to vaccination. Seropositive (S+) = Subjects with antibody concentration greater than or equal to (≥) 25 mIU/mL prior to vaccination. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination.	At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
Phase A: Immune Response to Measles With Respect to Anti-measles Antibody Concentrations in a Subset of Subjects	Anti-measles antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in milliinternational units per milliliter (mIU/mL).	At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
Phase A: Number of Subjects With Seroconversion/Seroresponse to Measles in a Subset of Subjects	Seronegative (S-) = Subjects with antibody concentration < 150 mIU/mL prior to vaccination. Seropositive (S+) = Subjects with antibody concentration ≥ 150 mIU/mL prior to vaccination. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination.	At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
Phase A: Immune Response to Mumps With Respect to Anti-mumps Antibody Concentrations in a Subset of Subjects	Anti-mumps antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in units per milliliter (U/mL).	At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
Phase A: Number of Subjects With Seroconversion/Seroresponse to Mumps in a Subset of Subjects	Seronegative (S-) = Subjects with antibody concentration < 231 U/mL prior to vaccination. Seropositive (S+) = Subjects with antibody concentration ≥ 231 U/mL prior to vaccination. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination.	At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
Phase A: Immune Response to Rubella With Respect to Anti-rubella Antibody Concentrations in a Subset of Subjects	Anti-rubella antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in International Units per milliliter (IU/mL).	At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
Phase A: Number of Subjects With a Seroconversion/Seroresponse to Rubella in a Subset of Subjects	Seronegative (S-) = Subjects with antibody concentration < 4 IU/mL prior to vaccination. Seropositive (S+) = Subjects with antibody concentration ≥ 4 IU/mL prior to vaccination. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination.	At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
Phase A: Number of Subjects With Confirmed Cases of Herpes Zoster	The number of subjects with confirmed cases of herpes zoster is reported.	From Day 0 until the end of Phase A (Year 2)
Phase A: Number of Subjects Reporting Fever	All fever = Occurrence of any fever (measured rectally) regardless of its intensity grade or relationship to vaccination. Related = fever (measured rectally) assessed by the investigator to be causally related to the study vaccination. Medical Advice = seek for medical advice.	Within 43 days (Day 0-42) post-vaccination period following each dose
Phase A: Number of Subjects Reporting Fever	All fever = Occurrence of any fever (measured rectally) regardless of its intensity grade or relationship to vaccination. Related fever = fever (measured rectally) assessed by the investigator to be causally related to the study vaccination. Medical Advice = seek for medical advice.	Within 15 days (Day 0-14) post-vaccination period following each dose
Phase A: Number of Subjects Reporting Solicited Local Symptoms	Solicited local symptoms assessed were pain, redness and swelling. Any solicited local symptom = Occurrence of any local symptom regardless of their intensity grade. Grade 3 pain = Cried when limb was moved/spontaneously painful. Grade 3 redness and swelling = greater than (>) 20 mm.	4 days post-vaccination period following each dose
Phase A: Number of Subjects Reporting Meningism	Any = Occurrence of meningism regardless of its intensity grade. Grade 3 meningism = Prevented normal, everyday activities. Related = Assessed by the investigator to be causally related to the study vaccination.	Within 43 days (Day 0-42) post-vaccination period following each dose
Phase A: Number of Subjects Reporting Parotitis	Any = Occurrence of parotitis regardless of its intensity grade. Grade 3 parotitis = Swelling with accompanying general symptoms. Related = Assessed by the investigator to be causally related to the study.	Within 43 days (Day 0-42) post-vaccination period following each dose
Phase A: Number of Subjects Reporting Rash	Any = Occurrence of rash regardless of its intensity grade. Grade 3 rash = 101-500 lesions. Grade 4 rash = > 500 lesions. Related rash = Assessed by the investigator to be causally related to the study vaccination.	Within 43 days (Day 0-42) post-vaccination period following each dose
Phase A: Number of Subjects With Suspected Sign of Meningism Including Febrile Convulsions	Any = Occurrence of meningism including febrile convulsions regardless of intensity grade.	Within 43 days (Day 0-42) post-vaccination period following each dose
Phase A: Number of Subjects Reporting Unsolicited Adverse Events (AEs)	Unsolicited AE assessed included any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any = Occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.	Within 43 days (Day 0-42) post-vaccination period following each dose
Phase A: Number of Subjects Reporting Serious Adverse Events (SAEs)	SAEs assessed included medical occurrences that resulted in death, were life-threatening, required hospitalisation or prolongation of hospitalisation or resulted in disability/incapacity. Any SAE = occurrence of SAE regardless of intensity grade or relation to vaccination.	From Day 0 until the end of Phase A (Year 2)
Phase A: Health Economics Analysis of Factors Leading to Indirect Costs Due to Varicella Illness	Parameters assessed: 1. Number of hours lost from work by parents/guardians as a result of taking care of their child due to varicella. 2. Number of hours the child lost attendance in: day care/childminder, school, or in any extra-curricular activities (e.g. sports or recreation or any type of organised leisure activities) due to varicella. 3. Number of hours spent by a nurse, a babysitter or any type of existing paid caregiver to look after the child (if applicable).	During Phase A (from Day 0 up to Year 2)
Phase B: Number of Subjects With Confirmed Varicella Case	Confirmed varicella case = A case that met the clinical case definition at least in the opinion of the investigator and was confirmed by laboratory test [PCR (+)] OR a case that met the clinical definition confirmed by the IDMC and was epidemiologically linked [Epi (+)] to a valid index case.	From the beginning of Phase B (Year 2) up to study end (Year 10)
Phase B: Number of Subjects With Moderate or Severe Confirmed Varicella Case	Confirmed varicella case = A case that met the clinical case definition at least in the opinion of the investigator and was confirmed by laboratory test [PCR (+)] OR a case that met the clinical definition confirmed by the IDMC and was epidemiologically linked [Epi (+)] to a valid index case. Moderately severe disease = 8-15 points; severe disease: ≥ 16 points (scored by IDMC using the modified Vázquez scale).	From the beginning of Phase B (Year 2) up to study end (Year 10)
Phase B: Number of Subjects With Probable or Confirmed Varicella Case	Probable or confirmed varicella = A case that met the clinical case definition (as determined by the IDMC) but was not laboratory confirmed [PCR (-)] AND was not epidemiologically linked [Epi (-)] to another probable or confirmed case.	From the beginning of Phase B (Year 2) up to study end (Year 10)
Phase B: Characteristics of Varicella Cases	Varicella cases were characterized by type, number and character of lesions, duration of rash, incidence of fever, systemic signs, the assessment by investigator, complications, treatment, outcome and intensity of severity.	From the beginning of Phase B (Year 2) up to study end (Year 10)
Phase B: Immune Response to Varicella Vaccine With Respect to Anti-Varicella Zoster Virus (Anti-VZV) Antibody Concentrations	Anti-VZV antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in milliinternational units per milliliter (mIU/mL).	At Year 4, Year 6, Year 8 and Year 10 time points
Phase B: Number of Subjects With Anti-VZV Antibody Concentrations Above the Cut-off Value	The anti-VZV antibody concentration cut-off value assessed was greater than or equal to (≥) 25 mIU/mL, in the sera of subjects seronegative before vaccination.	At Year 4, Year 6, Year 8 and Year 10 time points
Phase B: Immune Response to Measles With Respect to Anti-measles Antibody Concentrations	Anti-measles antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in milliinternational units per milliliter (mIU/mL).	At Year 4, Year 6, Year 8 and Year 10 time points
Phase B: Number of Subjects With Anti-measles Antibody Concentrations Above the Cut-off Value	The anti-measles antibody concentration cut-off value assessed was ≥ 150 mIU/mL, in the sera of subjects seronegative before vaccination.	At Year 4, Year 6, Year 8 and Year 10 time points
Phase B: Immune Response to Mumps With Respect to Anti-mumps Antibody Concentrations	Anti-mumps antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in units per milliliter (U/mL).	At Year 4, Year 6, Year 8 and Year 10 time points
Phase B: Number of Subjects With Anti-mumps Antibody Concentrations Above the Cut-off Value	The anti-mumps antibody concentration cut-off value assessed was ≥ 231 U/mL, in the sera of subjects seronegative before vaccination.	At Year 4, Year 6, Year 8 and Year 10 time points
Phase B: Immune Response to Rubella With Respect to Anti-rubella Antibody Concentrations	Anti-rubella antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in international units per milliliter (IU/mL).	At Year 4, Year 6, Year 8 and Year 10 time points
Phase B: Number of Subjects With Anti-rubella Antibody Concentrations Above the Cut-off Value	The anti-rubella antibody concentration cut-off value assessed was ≥ 4 IU/mL, in the sera of subjects seronegative before vaccination.	At Year 4, Year 6, Year 8 and Year 10 time points
Phase B: Characteristics of Zoster Cases	Zoster cases were characterized by number and character of lesions, duration of rash, incidence of fever, systemic signs, the assessment by investigator, complications, treatment, outcome and intensity of severity.	From 6 weeks after Dose 2 until study end (Year 10)
Phase B: Number of Subjects Reporting Serious Adverse Events (SAEs)	SAEs assessed included medical occurrences that resulted in death, were life-threatening, required hospitalisation or prolongation of hospitalisation or resulted in disability/incapacity. Any SAE = occurrence of SAE regardless of intensity grade or relation to vaccination.	From the beginning of Phase B (Year 2) up to study end (Year 10)
Phase B: Health Economics Analysis of Factors Leading to Indirect Costs Due to Varicella Illness	Parameters assessed: 1. Number of hours lost from work by parents/guardians as a result of taking care of their child due to varicella. 2. Number of hours the child lost attendance in: day care/childminder, school, or in any extra-curricular activities (e.g. sports or recreation or any type of organised leisure activities) due to varicella. 3. Number of hours spent by a nurse, a babysitter or any type of existing paid caregiver to look after the child (if applicable).	During Phase B

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Henry O, Brzostek J, Czajka H, Leviniene G, Reshetko O, Gasparini R, Pazdiora P, Plesca D, Desole MG, Kevalas R, Gabutti G, Povey M, Innis B. One or two doses of live varicella virus-containing vaccines: Efficacy, persistence of immune responses, and safety six years after administration in healthy children during their second year of life. Vaccine. 2018 Jan 8;36(3):381-387. doi: 10.1016/j.vaccine.2017.11.081. Epub 2017 Dec 7. Erratum In: Vaccine. 2018 Oct 29;36(45):6894.
• Prymula R, Bergsaker MR, Esposito S, Gothefors L, Man S, Snegova N, Stefkovicova M, Usonis V, Wysocki J, Douha M, Vassilev V, Nicholson O, Innis BL, Willems P. Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine versus one dose of monovalent varicella vaccine: a multicentre, observer-blind, randomised, controlled trial. Lancet. 2014 Apr 12;383(9925):1313-1324. doi: 10.1016/S0140-6736(12)61461-5. Epub 2014 Jan 29. Erratum In: Lancet. 2020 Jan 25;395(10220):272.
• Carryn S, Feyssaguet M, Povey M, Di Paolo E. Long-term immunogenicity of measles, mumps and rubella-containing vaccines in healthy young children: A 10-year follow-up. Vaccine. 2019 Aug 23;37(36):5323-5331. doi: 10.1016/j.vaccine.2019.07.049. Epub 2019 Jul 22.
• Habib MA, Prymula R, Carryn S, Esposito S, Henry O, Ravault S, Usonis V, Wysocki J, Gillard P, Povey M. Correlation of protection against varicella in a randomized Phase III varicella-containing vaccine efficacy trial in healthy infants. Vaccine. 2021 Jun 8;39(25):3445-3454. doi: 10.1016/j.vaccine.2021.02.074. Epub 2021 Mar 16.
• Povey M, Henry O, Riise Bergsaker MA, Chlibek R, Esposito S, Flodmark CE, Gothefors L, Man S, Silfverdal SA, Stefkovicova M, Usonis V, Wysocki J, Gillard P, Prymula R. Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine or one dose of monovalent varicella vaccine: 10-year follow-up of a phase 3 multicentre, observer-blind, randomised, controlled trial. Lancet Infect Dis. 2019 Mar;19(3):287-297. doi: 10.1016/S1473-3099(18)30716-3. Epub 2019 Feb 11. Erratum In: Lancet Infect Dis. 2020 Feb;20(2):e26.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2005
• Primary Completion (Actual): October 12, 2006
• Study Completion (Actual): October 12, 2006

Study Registration Dates

• First Submitted: September 23, 2005
• First Submitted That Met QC Criteria: September 23, 2005
• First Posted (Estimate): September 27, 2005

Study Record Updates

• Last Update Posted (Actual): September 23, 2019
• Last Update Submitted That Met QC Criteria: August 19, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Togaviridae Infections; Rubivirus Infections; Herpes Zoster; Chickenpox; Rubella
• Other Study ID Numbers: 100388; 104105 (EXT FU Y2) (Other Identifier: GSK); 103494 (EXT FU Y1) (Other Identifier: GSK); 104106 (EXT FU Y4-Y6-Y8-Y10) (Other Identifier: GSK); 2004-002676-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 100388
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 100388
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 100388
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 100388
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 100388
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 100388
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No